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• W2092026908 abstract "To assess the impact of laparoscopic surgery on ovarian reserve, we evaluated pre- and postoperative levels of serum anti-Müllerian hormone (AMH) in comparison with basal levels of FSH. The median AMH level was 2.98 ng/mL and 3.92 ng/mL before operation and was significantly reduced to a median level of 2.24 ng/mL and 3.29 ng/mL at 1 month after operation in the endometrioma group (n = 29) and the nonendometrioma group (n = 21), respectively, whereas postoperative basal FSH levels did not significantly change in comparison with preoperative levels. To assess the impact of laparoscopic surgery on ovarian reserve, we evaluated pre- and postoperative levels of serum anti-Müllerian hormone (AMH) in comparison with basal levels of FSH. The median AMH level was 2.98 ng/mL and 3.92 ng/mL before operation and was significantly reduced to a median level of 2.24 ng/mL and 3.29 ng/mL at 1 month after operation in the endometrioma group (n = 29) and the nonendometrioma group (n = 21), respectively, whereas postoperative basal FSH levels did not significantly change in comparison with preoperative levels. Laparoscopic ovarian cystectomy is currently considered the first-line treatment for benign ovarian tumors and cysts (1Alborzi S. Zarei A. Alborzi M. Management of ovarian endometrioma.Clin Obstet Gynecol. 2006; 49: 480-491Crossref PubMed Scopus (41) Google Scholar, 2Chapron C. Fauconnier A. Goffinet F. Breart G. Dubuisson J.B. Laparoscopic surgery is not inherently dangerous for patients presenting with benign gynaecologic pathology. Results of a meta-analysis.Hum Reprod. 2002; 17: 1334-1342Crossref PubMed Scopus (163) Google Scholar). However, the safety of a laparoscopic cystectomy has been questioned with respect to damage to the operated ovary. Ovarian reserve is defined as the functional potential of the ovary, which reflects the number and quality of the follicles left in the ovary at any given time. Over the years, various tests and markers of ovarian reserve have been reported. The static tests include serum markers, such as basal FSH, inhibin-B, and anti-Müllerian hormone (AMH), and ultrasonographic markers, such as ovarian volume and antral follicle count (AFC) (3Broekmans F.J. Kwee J. Hendriks D.J. Mol B.W. Lambalk C.B. A systematic review of tests predicting ovarian reserve and IVF outcome.Hum Reprod Update. 2006; 12: 685-718Crossref PubMed Scopus (921) Google Scholar, 4Maheshwari A. Fowler P. Bhattacharya S. Assessment of ovarian reserve—should we perform tests of ovarian reserve routinely?.Hum Reprod. 2006; 21: 2729-2735Crossref PubMed Scopus (82) Google Scholar). Anti-Müllerian hormone belongs to the transforming growth factor-β family and is produced by the granulosa cells of primary to small antral follicles (5Durlinger A.L. Gruijters M.J. Kramer P. Karels B. Ingraham H.A. Nachtigal M.W. et al.Anti-Müllerian hormone inhibits initiation of primordial follicle growth in the mouse ovary.Endocrinology. 2002; 143: 1076-1084Crossref PubMed Scopus (478) Google Scholar, 6Durlinger A.L. Kramer P. Karels B. de Jong F.H. Uilenbroek J.T. Grootegoed J.A. et al.Control of primordial follicle recruitment by anti-Müllerian hormone in the mouse ovary.Endocrinology. 1999; 140: 5789-5796Crossref PubMed Scopus (572) Google Scholar). Recently, it has been shown that the serum AMH levels may be a valuable marker of ovarian reserve (7Fanchin R. Schonauer L.M. Righini C. Guibourdenche J. Frydman R. Taieb J. Serum anti-Müllerian hormone is more strongly related to ovarian follicular status than serum inhibin B, estradiol, FSH and LH on day 3.Hum Reprod. 2003; 18: 323-327Crossref PubMed Scopus (532) Google Scholar, 8Kwee J. Schats R. McDonnell J. Themmen A. de Jong F. Lambalk C. Evaluation of anti-Müllerian hormone as a test for the prediction of ovarian reserve.Fertil Steril. 2008; 90: 737-743Abstract Full Text Full Text PDF PubMed Scopus (155) Google Scholar, 9McIlveen M. Skull J.D. Ledger W.L. Evaluation of the utility of multiple endocrine and ultrasound measures of ovarian reserve in the prediction of cycle cancellation in a high-risk IVF population.Hum Reprod. 2007; 22: 778-785Crossref PubMed Scopus (124) Google Scholar, 10Seifer D.B. MacLaughlin D.T. Christian B.P. Feng B. Shelden R.M. Early follicular serum müllerian-inhibiting substance levels are associated with ovarian response during assisted reproductive technology cycles.Fertil Steril. 2002; 77: 468-471Abstract Full Text Full Text PDF PubMed Scopus (430) Google Scholar), whereas the clinical value of testing for basal FSH, which is still used widely in clinical practice, was limited (11Bancsi L.F. Broekmans F.J. Mol B.W. Habbema J.D. te Velde E.R. Performance of basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: a meta-analysis.Fertil Steril. 2003; 79: 1091-1100Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar). Moreover, AMH is the only marker of ovarian reserve that is menstrual cycle independent and is unaffected by the use of oral contraceptive pills or GnRH agonists (12Seifer D.B. Maclaughlin D.T. Müllerian inhibiting substance is an ovarian growth factor of emerging clinical significance.Fertil Steril. 2007; 88: 539-546Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar). Therefore, serum AMH levels currently represent the most reliable and easily measurable maker for ovarian reserve. This study was conducted from January 2008 to December 2009 at the Department of Obstetrics and Gynecology of Nagoya University Hospital in Nagoya, Japan. Before enrollment, every patient was diagnosed as having uni/bilateral ovarian cysts or uterine leiomyomas. The inclusion criteria were as follows: [1] 18–45-year-old women with regular menstrual cycles (25–35 days), and [2] no evidence of any other endocrine disorders, including thyroid dysfunction, hyperprolactinemia, or Cushing's syndrome. Exclusion criteria were as follows: [1] previous history of adnexal surgery, [2] any suspicious findings of malignant ovarian disease, and [3] oral contraceptive use within 3 months before surgery. The study was approved by the institutional review board of Nagoya University Graduate School of Medicine, and informed consent was obtained from all patients. Laparoscopic pneumoperitoneum was induced by CO2 insufflation with an umbilical 12-mm trocar and was maintained at a pressure of 10 mm Hg. The removal of the cystic wall from the ovarian cortex or enucleation of uterine leiomyoma nodes was performed using grasping forceps and scissors. The wall of the cysts was stripped from the healthy surrounding normal ovarian tissue with the use of two atraumatic grasping forceps by traction and countertraction after identification of the cleavage plane. When necessary, hemostasis was achieved with bipolar forceps as minimally as possible, to avoid causing damage to normal tissues. Sutures were made for the closure of ovarian parenchyma or myometrium of the uterus. Blood samples were obtained from the patients at 2 weeks before surgery and 1 month after surgery between the third and seventh day in the consecutive cycles of menstruation. Serum was separated and stored at −80°C until assayed. Pre- and postoperative serum AMH concentrations were measured by an enzyme immunoassay kit according to the manufacturer's instructions (EIA AMH/MIS; Immunotech, Marseille, France) at the same time. The intra- and interassay coefficients of variation for the AMH assay were below 12.3% and 14.2%, respectively. The serum FSH concentrations were measured by an ELISA kit according to the manufacturer's instructions (Elegance FSH ELISA Kit; Bioclone, Marrickville, Australia). The intra- and interassay coefficients of variation for the FSH assay were, respectively, 3.4% and 4.2% at 6.9–20.3 IU/L, and 6.7% and 6.6% at 7.6–36.7 IU/L. Data were analyzed with the SigmaPlot 11 software program (Systat Software, San Jose, CA). We used the signed rank test to compare the concentrations of AMH and FSH before and after operation. A total of 65 patients were recruited, of whom 29 (unilateral 16, bilateral 13) had endometriomas, 21 (unilateral 16, bilateral 5) had nonendometriomas, and 15 had leiomyomas. The nonendometrioma group consisted of 18 mature cystic teratomas, 2 serous cyst adenomas, and 1 struma ovarii. Patient ages (mean ± SD) were 33.3 ± 5.0 years in the endometrioma group, 29.4 ± 7.3 years in the nonendometrioma group, and 36.2 ± 4.3 years in the leiomyoma group. No patients showed >15 mIU/mL serum FSH concentrations. Concentrations of serum FSH were not measured in the leiomyoma group because of preoperative administration of GnRH agonists. The median (range) level of preoperative serum AMH was 2.98 (0.48–12.1) ng/mL in the endometrioma group. The serum AMH levels after 1 month postoperatively significantly decreased (median 2.24, range 0.11–7.15 ng/mL; Fig. 1A ). The median levels of preoperative serum AMH were 3.92 (0.05–10.1) ng/mL and 4.64 (0.78–7.71) ng/mL in the nonendometrioma and leiomyoma groups, respectively. Smaller differences were observed, but statistically significant decreases in postoperative serum AMH levels were observed in the nonendometrioma and leiomyoma groups (median 3.29, range 0.07–9.05 ng/mL in the nonendometrioma group; median 4.16, range 0.36–5.81 ng/mL in the leiomyoma group). On the other hand, no significant differences in FSH levels were found between the preoperative and postoperative samples, either in the endometrioma group or in the nonendometrioma group (Fig. 1B). In a subgroup analysis of bilateral cystectomy, serum AMH levels, of which the preoperative median level was 3.04 (0.48–12.1) ng/mL, were significantly decreased in the endometrioma group (median 1.19, range 0.11–7.15 ng/mL; Fig. 1C). On the other hand, serum AMH levels did not significantly decrease either in the endometrioma group or in the nonendometrioma group in a subgroup analysis of unilateral cystectomy (Fig. 1D). We demonstrate that postoperative serum AMH levels significantly decreased compared with preoperative levels in patients with endometriomas and nonendometriomas. These results suggest that laparoscopic ovarian cystectomy itself might cause ovarian damage resulting in decreased ovarian reserve. However, we also found that there were smaller, but still significant, decreases in postoperative serum AMH levels in the leiomyoma group. Anesthesia drugs, surgical procedures of laparoscopic myomectomy, and/or preoperative use of GnRH agonist might be involved in the influence of ovarian function. Bleeding during myomectomy might have affected the follicle status in the ovaries. The basal FSH level has been widely accepted and used as an ovarian reserve marker. However, the clinical value of basal FSH is limited (11Bancsi L.F. Broekmans F.J. Mol B.W. Habbema J.D. te Velde E.R. Performance of basal follicle-stimulating hormone in the prediction of poor ovarian response and failure to become pregnant after in vitro fertilization: a meta-analysis.Fertil Steril. 2003; 79: 1091-1100Abstract Full Text Full Text PDF PubMed Scopus (173) Google Scholar). Our results indicate that basal FSH levels in these same patients did not rise postoperatively. Partridge et al. (13Partridge AH, Ruddy KJ, Gelber S, Schapira L, Abusief M, Meyer M, et al. Ovarian reserve in women who remain premenopausal after chemotherapy for early stage breast cancer. Fertil Steril 2009 Apr 29 [Epub ahead of print]Google Scholar) recently reported that serum AMH levels, but not basal FSH levels, significantly decrease in premenopausal women after chemotherapy for early-stage breast cancer in comparison with controls. Taken together, it seems that serum AMH level, and not basal FSH level, is a useful ovarian reserve marker in women with ovarian-invasive treatment. The AFC and ovarian volumes can also be used as indicators of ovarian reserve. However, it is difficult to assess the exact number of antral follicles and ovarian volume of the cystic ovary before cystectomy. Operative laparoscopy has been established as the gold-standard surgical approach in the treatment of endometriosis. On the other hand, Somigliana et al. (14Somigliana E. Vercellini P. Vigano P. Ragni G. Crosignani P.G. Should endometriomas be treated before IVF-ICSI cycles?.Hum Reprod Update. 2006; 12: 57-64Crossref PubMed Scopus (122) Google Scholar) discussed the possibility that cyst enucleation of ovarian endometriomas affects the number of oocytes retrieved in IVF cycles. However, the evaluation of ovarian reserve of an operated ovary by evaluating the ovarian response in infertile patients is biased by the selection of patients. Our data have been obtained from patients who have undergone laparoscopic cystectomy, and therefore suggest serum AMH to be a useful marker for the routine assessment of ovarian reserve after ovarian cystectomy. Despite the limited number of prospective trials, these studies demonstrated that the excision of endometriomas is more beneficial than drainage and electrocoagulation to avoid recurrence of endometriosis and related symptoms (15Alborzi S. Momtahan M. Parsanezhad M.E. Dehbashi S. Zolghadri J. A prospective, randomized study comparing laparoscopic ovarian cystectomy versus fenestration and coagulation in patients with endometriomas.Fertil Steril. 2004; 82: 1633-1637Abstract Full Text Full Text PDF PubMed Scopus (221) Google Scholar, 16Alborzi S. Ravanbakhsh R. Parsanezhad M.E. Alborzi M. Dehbashi S. A comparison of follicular response of ovaries to ovulation induction after laparoscopic ovarian cystectomy or fenestration and coagulation versus normal ovaries in patients with endometrioma.Fertil Steril. 2007; 88: 507-509Abstract Full Text Full Text PDF PubMed Scopus (68) Google Scholar, 17Beretta P. Franchi M. Ghezzi F. Busacca M. Zupi E. Bolis P. Randomized clinical trial of two laparoscopic treatments of endometriomas: cystectomy versus drainage and coagulation.Fertil Steril. 1998; 70: 1176-1180Abstract Full Text Full Text PDF PubMed Scopus (353) Google Scholar). However, our results indicate that a bilateral cystectomy of endometriomas severely decreases serum AMH levels, whereas a unilateral cystectomy maintains AMH levels similar to preoperative levels. Recently, Tsolakidis et al. (18Tsolakidis D. Pados G. Vavilis D. Athanatos D. Tsalikis T. Giannakou A. et al.The impact on ovarian reserve after laparoscopic ovarian cystectomy versus three-stage management in patients with endometriomas: a prospective randomized study.Fertil Steril. 2010; 94: 71-77Abstract Full Text Full Text PDF PubMed Scopus (162) Google Scholar) reported that serum AMH levels were less diminished after a three-step procedure of vaporization in comparison with an endometrioma cystectomy. All things considered, it is still necessary to assess which is beneficial, cystectomy or vaporization, as a fertility-preserving operation for endometriomas from the standpoint of ovarian reserve. In the present study, we demonstrated that laparoscopic cystectomy for endometriomas, especially bilateral cystectomy, caused a postoperative decrease of serum AMH levels compared with benign ovarian tumors and cysts. Our results suggest that serum AMH is a useful marker of ovarian reserve after ovarian cystectomy, although the association of decreased serum AMH levels with reproductive outcomes still remains to be investigated. It will therefore be necessary to investigate with a larger number of patients how and to what extent factors of endometriosis surgery, including types of instruments for electrocoagulation or cautery, size of endometriomas, score of endometriosis severity, amount of normal ovarian tissue excised, and blood loss during operation, contribute to diminished ovarian reserve. Chang et al. (19Chang H.J. Han S.H. Lee J.R. Jee B.C. Lee B.I. Suh C.S. et al.Impact of laparoscopic cystectomy on ovarian reserve: serial changes of serum anti-Mullerian hormone levels.Fertil Steril. 2010; 94: 343-349Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar) followed cases until 3 months after laparoscopic ovarian cystectomy and showed that serum AMH levels partially recovered. Therefore, it will be also necessary to investigate whether postoperative decreased AMH levels fully recover, and how long it would take. Consequently, future studies will optimize and individualize the surgical approach for endometriomas." @default.
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• W2092026908 title "Serum anti-Müllerian hormone level is a useful marker for evaluating the impact of laparoscopic cystectomy on ovarian reserve" @default.
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